{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:20:37Z","timestamp":1787642437522,"version":"build-2736575974"},"reference-count":27,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R00CA267180"],"award-info":[{"award-number":["R00CA267180"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL163168"],"award-info":[{"award-number":["R01HL163168"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["TR0018580"],"award-info":[{"award-number":["TR0018580"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Renal cell carcinoma (RCC) is a heterogeneous malignancy for which clear cell RCC (ccRCC) represents the most common and clinically aggressive subtype. Survivin (encoded by BIRC5), an inhibitor of apoptosis and key regulator of mitosis, is frequently overexpressed in RCC and associated with poor prognosis, yet its broader role in kidney cancer biology remains poorly defined. By analyzing transcriptomic data from The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC) cohort, we found that advanced-stage ccRCC exhibits widespread dysregulation of cell-cycle pathways, with 15,160 genes upregulated and 479 genes downregulated in stage IV compared to stage I tumors. To define survivin's functional contribution, we performed loss-of-function and pharmacologic inhibition studies in murine RENCA and human 786-O RCC cell lines. Survivin knockdown or treatment with the small-molecule inhibitor YM155 reduced proliferation, S-phase entry and cyclin D1 expression, and impaired collective (wound-healing), single-cell and transwell migration. Unexpectedly, survivin depletion increased mitochondrial content while lowering oxygen consumption, indicating accumulation of dysfunctional mitochondria. Together, these findings identify survivin as a node between cell-cycle progression and mitochondria in RCC.<\/jats:p>","DOI":"10.1242\/dmm.052706","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:35:07Z","timestamp":1787639707000},"source":"Crossref","is-referenced-by-count":0,"title":["Survivin drives renal cell carcinoma tumorigenesis via proliferative and metabolic adaptation"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2045-2466","authenticated-orcid":false,"given":"Shivani","family":"Tuli","sequence":"first","affiliation":[{"name":"University of Pittsburgh 1 Department of Bioengineering , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Inserra","sequence":"additional","affiliation":[{"name":"University at Buffalo 2 Department of Pathology and Anatomical Sciences , , Buffalo, NY 14260 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Murakami","sequence":"additional","affiliation":[{"name":"University of Pittsburgh 3 Department of Biology , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cais","family":"Vo","sequence":"additional","affiliation":[{"name":"University of Pittsburgh 3 Department of Biology , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1024-3877","authenticated-orcid":false,"given":"Sarvesh","family":"Senguttavan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh 1 Department of Bioengineering , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-1652","authenticated-orcid":false,"given":"Yongho","family":"Bae","sequence":"additional","affiliation":[{"name":"University at Buffalo 2 Department of Pathology and Anatomical Sciences , , Buffalo, NY 14260 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-3692","authenticated-orcid":false,"given":"Dave","family":"Gau","sequence":"additional","affiliation":[{"name":"University of Pittsburgh 1 Department of Bioengineering , , Pittsburgh, PA 15213 ,","place":["USA"]},{"name":"University of Pittsburgh 4 Department of Pathology , , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"2026082502350349000_DMM052706C1","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.3390\/molecules28031376","article-title":"Survivin small molecules inhibitors: recent advances and challenges","volume":"28","author":"Albadari","year":"2023","journal-title":"Molecules"},{"key":"2026082502350349000_DMM052706C2","doi-asserted-by":"publisher","first-page":"046108","DOI":"10.1063\/5.0150532","article-title":"Survivin as a mediator of stiffness-induced cell cycle progression and proliferation of vascular smooth muscle cells","volume":"7","author":"Biber","year":"2023","journal-title":"APL Bioeng."},{"key":"2026082502350349000_DMM052706C3","doi-asserted-by":"publisher","first-page":"314","DOI":"10.7150\/jca.13332","article-title":"Survivin and tumorigenesis: molecular mechanisms and therapeutic strategies","volume":"7","author":"Chen","year":"2016","journal-title":"J. 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Chem."},{"key":"2026082502350349000_DMM052706C8","doi-asserted-by":"publisher","first-page":"21137","DOI":"10.18632\/oncotarget.4121","article-title":"A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model","volume":"6","author":"Guo","year":"2015","journal-title":"Oncotarget"},{"key":"2026082502350349000_DMM052706C9","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1007\/s12013-014-0238-4","article-title":"Silencing of survivin using YM155 inhibits invasion and suppresses proliferation in glioma cells","volume":"71","author":"Guo","year":"2015","journal-title":"Cell Biochem. 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Biochem."},{"key":"2026082502350349000_DMM052706C14","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1002\/cncr.11851","article-title":"Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials","volume":"98","author":"Leibovich","year":"2003","journal-title":"Cancer"},{"key":"2026082502350349000_DMM052706C15","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1186\/s13046-021-02026-1","article-title":"Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1alpha, HIF2alpha, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma","volume":"40","author":"Li","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2026082502350349000_DMM052706C16","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2026082502350349000_DMM052706C17","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.ccr.2009.11.021","article-title":"IAP regulation of metastasis","volume":"17","author":"Mehrotra","year":"2010","journal-title":"Cancer Cell"},{"key":"2026082502350349000_DMM052706C18","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.3390\/ijms15022494","article-title":"Survivin as a preferential target for cancer therapy","volume":"15","author":"Mobahat","year":"2014","journal-title":"Int. J. Mol. 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